C-reactive protein (CRP) has long been known to appear in the blood during reactions in inflammation and tissue destruction. While structurally distinct from immunoglobulins, CRP shares with antibodies the ability to initiate precipitation, agglutination and complement consumption reactions and to promote phagocytosis. We now have observed CRP to induce C-dependent adherence, phagocytosis and cytolysis; to combine with and/or influence certain functions of T-lymphocytes, platelets, neutrophils, macrophages and basophils; and to show pronounced homology with the amyloid P component and distant homology with the immunoglobulins. Our major objective is to define the biological role of CRP in reactions of inflammation, repair, tissue destruction and resistance, with emphasis on its interrelationships with host defense mechanisms and its role in the acute phase response. To do so we proprose to evolve methods for large-scale purification and characterization of biologically active material; define aspects of the structure of CRP which relate to its function; delineate its interrelationships with its binding specificities and with the complement system, lymphocytes, granulocytes, macrophages and mast cells; define its interactions with normal and modified endogenous and exogenous membranes; investigate its appearance and reactivities in phylogenetic and ontogenetic perspectives; delineate its ability to initiate and/or modulate inflammatory reactions in experimental animals; begin to define its role in human disease and disease processes; and explore its interrelationships with other acute phase reactants in host defense and inflammation, with initial emphasis upon the amyloid P component and the alpha 1-acid glycoprotein. We hope in these ways to contribute to an understanding of the functions and role of CRP and the acute phase response in reactions of host defense, inflammation and disease, and to gain insight into new ways to interpret and manipulate these processes to clinical advantage.